IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells.
Genome-wide association (GWA) studies revealed a number of single nucleotide polymorphisms (SNPs) significantly associated with type 1 diabetes (T1D). In an attempt to confirm some of these candidate associations, we genotyped 2046 Caucasian patients and 2417 normal controls from the United States for SNPs in five genomic regions. While no evidence was obtained for four genomic regions (rs2929366/NM_144715 on chromosome 3, rs9127/Q7Z4C4 on chromosome 5, rs1445898/CAPSL on chromosome 5 and rs2302188/NM_033543 on chromosome 19), we provide strong evidence for association between T1D and multiple SNPs in the IFIH1 linkage disequilibrium (LD) block on chromosome 2q. Among the 10 SNPs genotyped for the 2q region, four SNPs located within the IFIH1 gene or at the 5' region of IFIH1 showed significant association with T1D in the Georgia population [odds ratio (OR) = 1.7-1.9] with the best P-value found at SNP rs1990760 (P = 8 x 10(-8) and OR = 1.9). Several SNPs outside of the IFIH1 gene also showed significant but weaker associations. Furthermore, IFIH1 gene expression levels in peripheral blood mononuclear cells are significantly correlated with IFIH1 genotypes, and higher IFIH1 levels are found in individuals with the susceptible genotypes (P = 0.005). Thus, both genetic association and gene expression data suggest that IFIH1 is the most plausible candidate gene implicated in T1D in this LD block.
Liu
Siyang
S
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, GA 30912, USA.
Wang
Hongjie
H
Jin
Yulan
Y
Podolsky
Robert
R
Reddy
M V Prasad Linga
MV
Pedersen
Jennifer
J
Bode
Bruce
B
Reed
John
J
Steed
Dennis
D
Anderson
Steve
S
Yang
Ping
P
Muir
Andy
A
Steed
Leigh
L
Hopkins
Diane
D
Huang
Yihua
Y
Purohit
Sharad
S
Wang
Cong-Yi
CY
Steck
Andrea K
AK
Montemari
Annalisa
A
Eisenbarth
George
G
Rewers
Marian
M
She
Jin-Xiong
JX
D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1